This Career Development Award (K01) will provide the candidate with the necessary skills to develop an independent research program focused on using population-based data to identify the psychological, physiological, and environmental mechanisms underlying the association between childhood adversity and the later onset of mood and anxiety disorders and to examine the role of genetic factors in altering developmental trajectories among children exposed to adversity. Although adverse childhood experiences, such as maltreatment and exposure to family violence, account for a substantial proportion of mental disorders in the population, the complex developmental pathways that underlie these associations remain poorly characterized. The overall aim of the current application is to test a developmental epidemiologic model that posits a central role of emotional and physiological reactivity as a mechanism linking childhood adversity to the subsequent onset of mood and anxiety disorders. The model predicts that childhood adversity is more likely to trigger heightened emotional reactivity among individuals with specific genetic polymorphisms that increase vulnerability to stress. The training plan is designed to provide the candidate with skills in developmental psychopathology, stress biology and psychophysiology, and genetic epidemiology. Specifically, the candidate will acquire the knowledge and skills to: a) conduct developmentally informed studies to identify psychological and physiological mechanisms linking childhood adversity to mood and anxiety disorders; b) design, conduct, and analyze genetically informative studies; c) identify biologically plausible phenotypes that link genotype, childhood adversity, and mood and anxiety disorders; and d) conduct prospective epidemiologic studies of individuals exposed to childhood adversities, which assess both genetic and environmental risk factors. These skills will be developed through a combination of didactic training, guided readings, and mentored research projects. The proposed research program involves a combination of original data collection and analysis of existing epidemiologic data. The candidate will collect psychopathology, psychophysiology, experience sampling, and genetic data from a community sample of adolescents to examine the central hypotheses of the conceptual model. Psychophysiology methods and a candidate gene approach will be used to define a potential phenotype involving heightened emotional and physiological reactivity that links genetic vulnerability, childhood adversity exposure, and mood and anxiety disorders. The conceptual model also will be tested through analysis of three longitudinal epidemiologic data sets: the National Comorbidity Survey II, the Avon Longitudinal Study of Children and Parents, and the Nurses' Health Study II, two of which measure both genetic and environmental risk factors. Training activities and results will be used to develop an R01 application for a prospective epidemiologic study that assesses both genetic and environmental risk factors and aims to identify developmental pathways linking childhood adversity to the onset of mood and anxiety disorders. PUBLIC HEALTH RELEVANCE: The proposed research aims to identify psychological and physiological mechanisms underlying the association between childhood adversity and the later onset of mood and anxiety disorders and to determine whether genetic polymorphisms associated with the stress response system modify developmental trajectories among individuals exposed to childhood adversity, including maltreatment and family violence. Elucidation of these mechanisms, and the role of genetic vulnerability in altering mediating pathways, is critical to inform the development of preventive interventions targeting children exposed to adversity. Given that a substantial proportion of mental disorders in the population are directly attributable to childhood adversity, the development of such interventions represents an important public health priority.